Clonidine Versus Chloral Hydrate for Recording Sleep EEG in Children.

Objective One of the difficulties to conduct electroencephalography (EEG) in pediatric patient population is that they are not always cooperative during the procedure. Different medications are used to induce sedation during EEG recording. In order to find a medication with the least adverse effects and high efficacy, the current study aimed at comparing clonidine and chloral hydrate as a premedication prior to EEG recording in pediatric population. Materials & Methods A prospective, randomized, single-blinded, controlled trial was conducted on 198 children (9 to 156 months old) to investigate the sedative and adverse effects of clonidine and chloral hydrate. Patients, partially sleep-deprived the night before, were randomly divided into two groups of clonidine (n=100) and chloral hydrate (n=98) on an alternative day basis. Results The average sleep onset latency was significantly longer in the clonidine group than chloral hydrate group (the Mann-Whitney test, p <0.0001). Sleep duration ranged 15 to 150 minutes and it was not significantly different between the two groups (the Mann-Whitney test, p = 0.2). Drowsiness terminated faster with chloral hydrate than clonidine. Drowsiness after arousal was observed in 58% and 26.1% of patients in the clonidine and chloral hydrate groups, respectively; the difference between the groups was signiﬁcant (the Mann-Whitney test, p = 0.058). EEG results were reported normal in 77 subjects in the chloral hydrate group (77%) and 69 subjects (69%) in the clonidine group (p = 0.161). Generalized epileptiform discharges were significant in the clonidine group (the Mann-Whitney test, p = 0.006). Conclusion The results of the current study showed that both 5% chloral hydrate (1 mL/kg) and clonidine (4 μg/kg) could be administered as a premedication prior to EEG recording in children, although drowsiness after arousal was higher with clonidine than chloral hydrate. However, the yield of generalized epileptiform discharges in the clonidine group was greater than that of the chloral hydrate group.


Introduction
One of the difficulties to conduct electroencephalography (EEG) in pediatric population is that they are not always cooperative during the procedure. It is generally agreed that most children undergoing medical procedures get frightened and uncooperative, and should be managed with behavioral and non-pharmacologic techniques. Unfortunately, a small percentage of pediatric patients cannot be successfully managed solely with such techniques (1). Several sedativehypnotic agents can be used in children for medical procedures including benzodiazepines, ketamine, hydroxyzine, melatonin, clonidine, chloral hydrate, sufentanil, dexmedetomidine, etc.
Clonidine, an α-2 agonist, is suggested as an alternative agent for sleep induction in children. , (2) concluded in a review study that clonidine, administered via oral, rectal, or caudal route is a promising adjunct to anesthetics and analgesics to enhance the quality of perioperative care in infants and children.
Later publications also support the utilization of clonidine as premedication (3).
Chloral hydrate has some known adverse effects such as nausea, vomiting, agitation, ataxia, prolonged sedation, delayed apnea events,

Conclusion
The results of the current study showed that both 5% chloral hydrate (1 mL/kg) and clonidine (4 μg/kg) could be administered as a premedication prior to EEG recording in children, although drowsiness after arousal was higher with clonidine than chloral hydrate. However, the yield of generalized epileptiform discharges in the clonidine group was greater than that of the chloral hydrate group.
A number of previous studies compared sedative and adverse effects of some premedication such as midazolam, melatonin and chloral hydrate, but there is still a lack of studies on comparing clonidine with chloral hydrate. The current prospective, randomized, single-blinded, controlled trial aimed at comparing the sedative and adverse effects of clonidine and chloral hydrate.

Materials & Methods
The protocol of the current prospective study was approved by the Ethics Committee of Tehran University of Medical Sciences. Written and oral informed consent was obtained from parents prior to inclusion in the study. The current study was conducted over one year at a major pediatric university hospital in Tehran, Iran. The enrolled subjects were children within the age range of 9 to 156 months scheduled for EEG recording in the center. The study had a randomized, single-blinded design; patients were randomly allocated to one of the two premedication options of oral clonidine or chloral hydrate.
The following data were obtained: age, gender, weight, EEG indication, underlying medical
The two groups were matcher for gender. The

Efficacy of premedication
The time gap between premedication and the start

Figure 1. Sleep Characteristics in the Chloral Hydrate and Clonidine Groups
Iran J Child Neurol. winter 2020 Vol. 14 No. 1

Discussion
Children undergoing EEG may experience significant anxiety and distress during the procedure, but the question whether routine premedication for children prior to EEG is necessary or not is currently under debate.
Hatava and Olsson showed that pre-operative psychological preparation and the presence of parents were beneficial and could reduce the need for pharmacological premedication (7). However, sedative premedication with midazolam was more effective than either parental presence or no intervention at all to manage child/parent anxiety during the pre-operative period (8,9). According to these facts, researchers are looking for the best medication to induce sleep during EEG in children.
An ideal medication for this goal should have rapid onset, long-acting sedative effect, low side effects, and the minimum impact on the EEG background (8). Benzodiazepines are drugs most widely used as premedication in pediatric anesthesia, and midazolam is at the top of the list of benzodiazepines used for induction of sedation in children (10).
Midazolam, when used as the premedication in children, has a number of beneficial effects such as effective sedation, rapid onset, short acting, lower rate of vomiting, and less amnesia after sedation (11)(12)(13); although some paradoxical reactions such as agitation (14,15) and hypotonia (8)  In the current study, there was no significant difference in gender distribution between the two groups, although the mean age of the subjects in the clonidine group was higher.
One important factor as premedication agent in EEG recording is its impact on EEG interpretation.
According to EEG results, normal EEG was was not seen in this study (16). Additionally, no respiratory failure or hypoxia was observed using these drugs, although infants younger than six months of age were excluded from the study.